Ghrelin and leptin elevation in postoperative intra-abdominal sepsis

Both ghrelin and leptin are important signals in the regulation of food intake and energy balance. Leptin concentrations are elevated in the majority of obese individuals, and its levels usually correlate with adiposity and body mass index. Ghrelin as a new growth hormone (GH)-releasing peptide was discovered in 1999. Ghrelin stimulates food intake and exhibits gastroprotective properties. Many other regulatory effects of both ghrelin and leptin involving cardiovascular, gastrointestinal, renal, and endocrine systems were revealed. New experimental studies show both hormones as new acute phase reactants in animal models of inflammatory reaction. The aim of this study was to characterize the levels of circulating ghrelin and leptin in relation to systemic inflammatory response. We used a postoperative bacterial sepsis after large abdominal surgery as a model of cytokine network hyperstimulation.

The prospective study was performed on 25 surgical patients with proven postoperative intra-abdominal sepsis after large abdominal surgery. Plasma levels of ghrelin (RIA), leptin, TNF-alpha, IL-1beta, sIL-2R, IL-6 (ELISA analysis), CRP and alpha1-antitrypsin (nephelometric analysis) were analyzed.

Authors demonstrate statistically significant elevation of plasma ghrelin (492.3+/-70.6 ng/l) and leptin (31.6+/-12.2 microg/l) compared with the control group (336.5+/-46,1, p<0.01 for ghrelin, 3.5+/-1.2 microg/l, p<0.001 for leptin). The regression coefficient was the highest for ghrelin and IL-6 (r=0,44, p<0.05), and for ghrelin and TNF (r=0.43, p<0.05) in the sepsis group. In regard to leptin, the regression coefficient was the highest for IL-6 and leptin (r=0.53, p<0.05) and for leptin and CRP (r=0.51, p<0.05). There was no significant correlation between ghrelin and IL-1beta, ghrelin and sIL-2R, and leptin and IL-1beta.

During postoperative intra-abdominal sepsis, both ghrelin and leptin plasma levels are elevated and positively correlate with both inflammatory cytokines (TNF-alpha, IL-6) and main APP member (CRP). It supports experimental finding that TNF-alpha and IL-6 can be important regulatory factors of their synthesis. This hormonal reaction is not specific to sepsis--the significant increase of both ghrelin and leptin occurs during an uncomplicated postoperative response, although in a lesser extent than was shown in sepsis.